Suenaert Peter, Bulteel Veerle, Vermeire Severine, Noman Maja, Van Assche Gert, Rutgeerts Paul
Division of Gastroenterology, Montreal General Hospital, McGill University Health Centre, McGill University, Montreal, Quebec, Canada.
Inflamm Bowel Dis. 2005 Jul;11(7):667-73. doi: 10.1097/01.mib.0000168371.87283.4b.
Crohn's disease (CD) is associated with gut barrier dysfunction. Besides the baseline barrier defect, a subgroup of patients also expresses an intestinal barrier hyperresponsiveness to nonsteroidal anti-inflammatory drugs. We studied whether reducing inflammation and restoring gut barrier dysfunction with anti-tumor necrosis factor (TNF) antibody treatment also antagonizes the permeability increase by oral nonsteroidal anti-inflammatory drug intake in patients with CD.
Thirty-one healthy control subjects and 25 patients with active CD were studied. The 31 controls performed intestinal permeability testing for Cr-EDTA before (baseline) and after oral intake of indomethacin (50 + 75 mg). Twenty-five patients carried out a baseline and indomethacin-mediated permeability test before infliximab infusion. The patients repeated either the indomethacin test (12/25) or baseline and indomethacin tests (13/25), 1 month after this treatment. Intestinal permeability was studied by measurement of urinary excretion of Cr-EDTA after oral intake.
Increased whole gut permeation before treatment (3.16%; interquartile range [IQR], 2.92-5.72) was restored to normal values (2.47%; IQR, 1.97-2.78) by anti-TNF treatment. Indomethacin increased whole gut permeability significantly more in patients with CD (before anti-TNF: 6.50%; IQR, 4.84-10.38; after anti-TNF: 5.50%; IQR, 3.97-10.09) compared with the healthy subjects (4.66%; IQR, 3.51-5.64). Eleven of 25 patients (44%) had an abnormal whole gut permeability response to indomethacin before anti-TNF, and 9 of them remained hyperresponsive after infusion, despite clinical remission.
Although anti-TNF treatment suppresses inflammation and restores gut barrier function in patients with CD, it does not antagonize the barrier hyperresponsiveness to indomethacin. These data support the notion of an underlying intestinal mucosal barrier hyperresponsiveness in a subset of patients with CD, independent of inflammation.
克罗恩病（CD）与肠道屏障功能障碍有关。除了基线屏障缺陷外，一部分患者还表现出肠道屏障对非甾体抗炎药的高反应性。我们研究了使用抗肿瘤坏死因子（TNF）抗体治疗减轻炎症并恢复肠道屏障功能障碍是否也能拮抗CD患者口服非甾体抗炎药引起的通透性增加。
研究了31名健康对照者和25名活动期CD患者。31名对照者在口服吲哚美辛（50 + 75 mg）之前（基线）和之后进行了铬标记乙二胺四乙酸（Cr-EDTA）的肠道通透性测试。25名患者在英夫利昔单抗输注之前进行了基线和吲哚美辛介导的通透性测试。在该治疗1个月后，12名患者重复进行吲哚美辛测试（25名患者中的12名），13名患者重复进行基线和吲哚美辛测试（25名患者中的13名）。通过测量口服后尿中Cr-EDTA的排泄来研究肠道通透性。
抗TNF治疗使治疗前增加的全肠道通透性（3.16%；四分位间距[IQR]，2.92 - 5.72）恢复到正常水平（2.47%；IQR，1.97 - 2.78）。与健康受试者（4.66%；IQR，3.51 - 5.64）相比，吲哚美辛使CD患者的全肠道通透性增加更为显著（抗TNF治疗前：6.50%；IQR，4.84 - 10.38；抗TNF治疗后：5.50%；IQR，3.97 - 10.09）。25名患者中有11名（44%）在抗TNF治疗前对吲哚美辛的全肠道通透性反应异常，其中9名患者在输注后尽管临床缓解但仍保持高反应性。
尽管抗TNF治疗可抑制CD患者的炎症并恢复肠道屏障功能，但它并不能拮抗对吲哚美辛的屏障高反应性。这些数据支持了一部分CD患者存在潜在的肠道黏膜屏障高反应性这一观点，且该反应与炎症无关。
